Developing macrophage-based technologies for tissue regeneration. Different tissues show distinct regenerative capacities with an organism and across the phylogeny. What underlies this diversity in regenerative ability at cellular and molecular level is far from clear. Building on foundational discoveries in zebrafish, this study seeks to determine if this capacity could, in part, be explained through the properties of a component of the innate immune system, the macrophage, which preliminary da ....Developing macrophage-based technologies for tissue regeneration. Different tissues show distinct regenerative capacities with an organism and across the phylogeny. What underlies this diversity in regenerative ability at cellular and molecular level is far from clear. Building on foundational discoveries in zebrafish, this study seeks to determine if this capacity could, in part, be explained through the properties of a component of the innate immune system, the macrophage, which preliminary data shows generates a transient pro-regenerative muscle stem cell niche in zebrafish. This study will determine if macrophage subtypes acts to coordinate regeneration in other tissues and systems and if a programable pro-regenerative cell can be made in vitro that stimulate regeneration in different settings.Read moreRead less
Elucidating the mechanisms of mitochondrial DNA escape. The human body is powered by mitochondria, microscopic components of living cells that make the energy they need to function. Mitochondrial damage is linked to a wide spectrum of human diseases, from devastating syndromic illnesses to neurodegeneration and autoimmunity. This project is focused on 1) how stresses such as cancer therapy or infection cause mitochondrial damage, and 2) understanding the biological processes that are triggered i ....Elucidating the mechanisms of mitochondrial DNA escape. The human body is powered by mitochondria, microscopic components of living cells that make the energy they need to function. Mitochondrial damage is linked to a wide spectrum of human diseases, from devastating syndromic illnesses to neurodegeneration and autoimmunity. This project is focused on 1) how stresses such as cancer therapy or infection cause mitochondrial damage, and 2) understanding the biological processes that are triggered inside the cell as it tries to recover. It will give a much greater understanding of mitochondrial damage at the microscopic level, and has the potential to unlock new avenues of investigation into the causes of inflammatory and immune disorders.Read moreRead less
Investigation of the molecular machinery enabling phage to enter bacteria. This project aims at a comprehensive understanding of the architecture of a biological nanomachine, called a phage, through broad-reaching investigation into how the component parts to work together to function in attacking bacteria. The discovery project takes the foundation knowledge of each of the component parts, builds a conceptual framework using breakthrough technology to address the precise architecture of the com ....Investigation of the molecular machinery enabling phage to enter bacteria. This project aims at a comprehensive understanding of the architecture of a biological nanomachine, called a phage, through broad-reaching investigation into how the component parts to work together to function in attacking bacteria. The discovery project takes the foundation knowledge of each of the component parts, builds a conceptual framework using breakthrough technology to address the precise architecture of the component parts within the nanomachine. The project aims to expand Australia’s knowledge base and research capability in the research frontier of nanomachines. This ground-breaking research program provides unique training opportunities for research students and staff in projects driving frontier technology applications.Read moreRead less
An investigation into flagellotropic bacteriophage stability and biology. This project aims to understand the capabilities of a type of virus called bacteriophage (phage). Significant economic loss in the food industry has led the USA and Europe to deploy phage to decontaminate food-processing machinery. These phage kill food-spoiling bacteria. This project expects to fill gaps in our knowledge, particularly to assit in choosing phage that are of increased stability and thus more long-lasting fo ....An investigation into flagellotropic bacteriophage stability and biology. This project aims to understand the capabilities of a type of virus called bacteriophage (phage). Significant economic loss in the food industry has led the USA and Europe to deploy phage to decontaminate food-processing machinery. These phage kill food-spoiling bacteria. This project expects to fill gaps in our knowledge, particularly to assit in choosing phage that are of increased stability and thus more long-lasting for deployment in industrial settings, and to inform additives to the phage preparations to increase their potency in killing bacteria. The project should provide significant benefits in training students and staff in methodology for investigating phage for future applications in Australian industry and biotechnology.
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Formation and clearance of endothelial cell-derived exophers. This project aims to investigate how cells that line the blood vessels release cellular wastes and their subsequent removal by immune cells.
It is critical that cellular waste are removed in a timely manner as their accumulation inside the cell can interfere with normal cell functions. The intended outcome of the project is to generate fundamental new knowledge of the mechanisms by which cellular waste are efficiently removed.
Exp ....Formation and clearance of endothelial cell-derived exophers. This project aims to investigate how cells that line the blood vessels release cellular wastes and their subsequent removal by immune cells.
It is critical that cellular waste are removed in a timely manner as their accumulation inside the cell can interfere with normal cell functions. The intended outcome of the project is to generate fundamental new knowledge of the mechanisms by which cellular waste are efficiently removed.
Expected outcomes encompass a paradigm-shift in understanding how cells that line the blood vessels dispose unwanted cellular contents. This should provide significant benefits including understanding how these specialised cells maintain the integrity of blood vessels and communicate with immune cells.Read moreRead less
Autocyclases: A new class of self-cyclising proteins. The biotechnology sector is emerging as an important economic strength in Australia. While the improved efficacy and selectivity of biomolecules has seen them emerge as alternatives to existing chemicals in health and agriculture, the stability of biomolecules remains a major limiting factor. A general strategy for improving protein stability is by joining the ends of the peptide chain in a cyclisation reaction. While a wide range of cyclic p ....Autocyclases: A new class of self-cyclising proteins. The biotechnology sector is emerging as an important economic strength in Australia. While the improved efficacy and selectivity of biomolecules has seen them emerge as alternatives to existing chemicals in health and agriculture, the stability of biomolecules remains a major limiting factor. A general strategy for improving protein stability is by joining the ends of the peptide chain in a cyclisation reaction. While a wide range of cyclic peptides and proteins are being developed in Australia and around the world, the cyclisation reaction presents a significant challenge. In this proposal we detail a novel method for protein cyclisation as a general, low-cost and green production method for making a diverse range of biomolecules. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE240101210
Funder
Australian Research Council
Funding Amount
$375,837.00
Summary
A liquid protein platform for dynamic bio-inspired reaction compartments. This project aims to investigate liquid protein as a novel material for biotechnology by producing protein droplets with a range of material and structural properties and assess the activity of internalised enzymes. The project will combine concepts from protein-based subcellular super-structure and enzyme protein structure and apply cutting-edge biochemistry methods to study how catalysis can be controlled and directed th ....A liquid protein platform for dynamic bio-inspired reaction compartments. This project aims to investigate liquid protein as a novel material for biotechnology by producing protein droplets with a range of material and structural properties and assess the activity of internalised enzymes. The project will combine concepts from protein-based subcellular super-structure and enzyme protein structure and apply cutting-edge biochemistry methods to study how catalysis can be controlled and directed through liquid protein design. Expected outcomes include a new platform for using protein droplets to engineer dynamic catalytic compartments, strong international and interdisciplinary collaborations, and a knowledge-base for building synthetic biology tools and technologies for future green chemistry-based industries.Read moreRead less
Understanding how cells regulate self eating during starvation and stress. This project aims to investigate how autophagosomes are built during autophagy by using advanced multi-modal imaging and unique gene-edited human cell lines. This project expects to generate new knowledge on how a family of evolutionary conserved proteins regulate autophagosome formation during starvation and stress conditions. Expected outcomes include the development of frontier imaging technologies that can be subseque ....Understanding how cells regulate self eating during starvation and stress. This project aims to investigate how autophagosomes are built during autophagy by using advanced multi-modal imaging and unique gene-edited human cell lines. This project expects to generate new knowledge on how a family of evolutionary conserved proteins regulate autophagosome formation during starvation and stress conditions. Expected outcomes include the development of frontier imaging technologies that can be subsequently utilised for the advancement of any field of cell biology. This should provide significant benefits by placing Australia at the forefront of cell biology technologies and increasing our understanding of how plant and human cells can protect themselves during starvation and stress.
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Engineering self-assembled intracellular biological condensates. Cells depend on proteins linking together to build cellular structure, but how weak interactions build stable structure is a mystery. New evidence suggests proteins come together and then change state, employing liquid-like behaviour that builds vital nanoscale structure, such as nuclear bodies called paraspeckles. This project will unlock the secrets of this mysterious behavior of proteins, using paraspeckles as a model. We will u ....Engineering self-assembled intracellular biological condensates. Cells depend on proteins linking together to build cellular structure, but how weak interactions build stable structure is a mystery. New evidence suggests proteins come together and then change state, employing liquid-like behaviour that builds vital nanoscale structure, such as nuclear bodies called paraspeckles. This project will unlock the secrets of this mysterious behavior of proteins, using paraspeckles as a model. We will use this information for nanotechnology application to build a synthetic paraspeckle inspired structure with bespoke function. Benefits will include new concepts in how vital cell structure is assembled and disassembled, and nanotechnology and synthetic biology tools to manipulate cellular processes.Read moreRead less